This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Driven by imaging data from existing and planned imaging experiments in our laboratory and through collaborations within the Cell Migration Consortium, we are building a spatial model of PI3K/RFG co-regulation at the whole-cell level. A phenomenological model of signaling-protrusion coupling will be constructed, guided by analysis of live-cell imaging experiments. To the extent possible, we will develop the model, or modules thereof, in the Virtual Cell environment. The Haugh group has previously made use of the new membrane diffusion capabilities of VCell in our work on gradient sensing, and these models are publicly available to other VCell users. Cell mechanical modeling capabilities, currently under development by the VCell team in collaboration with the CMC modeling initiative, will be utilized in this project as they become available. These will depend on the elliptic solver planned for the next NRCAM project period. Incorporation of mechanics into the VCell framework will then be facilitated by the newly proposed multiphysics layer and plug-in architecture.